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Salmonella-mediated delivery of Francisella type VI secretion system proteins as antigens to induce protective immunity

Award Number: R21AI190648
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/23/2025
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Salmonella-mediated delivery of Francisella type VI secretion system proteins as antigens to induce protective immunity - PROJECT SUMMARY/ABSTRACT Bacterial pathogens employ a myriad of mechanisms to invade the host, evade immune responses and inflict damage. Arguably the most pathogenic bacterium known is Francisella tularensis, which boasts a mortality rate upwards of 60%, is transmitted via aerosols, and can be made antibiotic resistant through rudimentary methods. Based on these characteristics, F. tularensis is one of only three bacteria of highest concern for weaponization by the Centers for Disease Control and Prevention. Although these bacteria have been studied since the early 1900s, we still lack a protective and non-toxic vaccine. These intracellular bacterial pathogens employ a contractile toxin secretion apparatus called the type VI secretion system (T6SS) to inject effector proteins into host cells to facilitate invasion into the cytosol and proliferation. Deleting any component of the T6SS apparatus or the effector proteins that it secretes renders Francisella avirulent. In this application, we propose to use an established antigen delivery strain of Salmonella to insert Francisella T6SS proteins directly into phagocytic cells to induce protective immunity. The protective immunity enhanced Salmonella vaccines (PIESVs) are composed of S. Typhmurium strains that simultaneously induce antigen expression and self-destruct within 8-10 cell divisions in the host. This results in antigen delivery into phagocytic cells within lymphoid tissue and has been used extensively as an antigen delivery platform. We will construct PIESV strains that express T6SS proteins and determine if they can elicit protective immunity in a mouse model for Francisella infection. These studies will provide insight into antigens that are protective against subsequent infection.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $422,125 )
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Allergy and Infectious Diseases Research	000	1	7/23/2025	NEW	$422,125
														Subtotal = $422,125

Grand Total All Awards = $422,125

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Salmonella-mediated delivery of Francisella type VI secretion system proteins as antigens to induce protective immunity

Award Number: R21AI190648

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/23/2025

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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